Cytokine release syndrome (CRS) is a well-documented toxicity associated with immunotherapies, particularly chimeric antigen receptor (CAR)-modified T cells, and tocilizumab, a monoclonal Ab directed against the interleukin-6 (IL-6) receptor, has been effectively utilized for the management of CRS associated with CAR-T therapy. A febrile syndrome attributed to cytokine elaboration by proliferating T cells has similarly been reported in the setting of haploidentical PBSC transplant (PBSCT). Here, we report a case of grade 3 CRS emerging as a complication of haploidentical PBSCT, successfully treated with tocilizumab. The patient was a 42-yr-old man with primary refractory stage IVB Hodgkin lymphoma with involvement of the bone and pleura, and suspected involvement of the lung parenchyma. He was admitted for hematopoietic stem cell transplantation (HSCT) from his haploidentical brother; as the donor was deemed ineligible for bone marrow harvest, a PBSC graft was planned. On day 0, the patient received the haploidentical PSBC graft containing 5 × 106 CD34+ cells/kg and 2.06 × 108 CD3+ cells/kg uneventfully. Approx. 12 h after allograft infusion, the patient became febrile with associated mild tachycardia and new diarrhea, but he was normotensive with adequate oxygenation on room air. Chest X-ray showed a new left base consolidation with associated trace left pleural effusion. He eventually developed worsening tachycardia to the 120s, relative hypotension to SBP 90s, tachypnea with respiratory rate in the 20s and desaturation to 87%. There was new acute kidney injury with serum creatinine of 1.9 mg/dL (from 0.8 mg/dL 1 day prior). Serum C-reactive protein (CRP) was found to be 15 mg/dL, and IL-6 found to be 1113.60 pg/mL. Given suspicion for CRS, the patient received tocilizumab 4 mg/kg on day +2. Corticosteroids were not used as it is standard to avoid them prior to giving cyclophosphamide in this transplant setting. On days +3 and +4, he received cyclophosphamide 50 mg/kg per day as planned. He initially remained febrile, required up to 5 L of supplemental oxygen, and was briefly hypotensive to the 80s/50s. By the evening of day +3, he had defervesced, with normalization of hemodynamics and decreasing oxygen requirement. At outpatient follow-up 1 mo after transplant, CRP remained stable at 4.06 mg/dL and IL-6 had declined to 41.6 pg/mL. As the use of haploidentical transplantation increases, issues regarding the finer points of this approach-including optimal conditioning, graft source and management of its unique toxicities-will merit ongoing consideration. Details regarding the incidence, clin. presentation and management of CRS including the use of tocilizumab during haploidentical PBSCT represent important areas for further discourse. Supporting the role of cytokine release in this syndrome, fevers have reportedly resolved in most cases after post-transplant cyclophosphamide administration. In the current example, the time course of clin. improvement, with resolution of fevers ∼24 h after tocilizumab and only 12 h after the patient's first dose of cyclophosphamide, suggests that the former had a larger role in the immediate term. Consideration of CRS including standardized procedures for the measurement of inflammatory cytokine levels will allow for the rapid diagnosis and management of this potentially severe complication of haploidentical transplantation, particularly when PBSC grafts are required.